Hepatitis C virus is both expensive to treat and a significant cause of morbidity and mortality. To further understand the virological determinants of infection and the development of chronicity, the hepatitis C virus sequence in the early stages of infection has been determined from the same patients. In particular the sequencing effort is focused on the viral sequence before and after treatment, in the two patients who were HIV positive and relapsed. The complete sequence has been determined and has been analyzed. A manuscript is being drafted. A second project entails obtaining portal blood in patients with chronic hepatitis C infection. Patients are then treated for hepatitis C and portal blood is obtained after treatment and clearance. The intention of this study is to understand factors that may cause liver disease progression in patients with hepatitis C. The protocol is fully enrolled and the second set of portal blood sampling has now been obtained. Laboratory analysis is complete and data are currently being analyzed. A second type of chronic hepatitis studied is hepatitis D. Hepatitis D is the most aggressive form of viral hepatitis as well as the most difficult to treat. Interferon therapy is the standard approach. Patients are typically treated for 6 months to a year. Relapse after cessation of therapy is the norm. A second treatment trial for hepatitis D has been initiated with a prenylation inhibitor. Both phases of this study have been completed with 14 patients treated. The results are now published. The therapy was shown to have promise and to be safe when given for 28 days. A second study with a prenylation inhibitor was then initiated, fully enrolled, and the treatment phase is now complete. Treatment was for 3 - 6 months. Patients have completed the follow up phase. Results are currently being analyzed and a manuscript is in preparation. A follow up study has just begun enrollment to treat patients with a prenylation inhibitor, ritonavir, and lambda interferon. This study is now fully enrolled and patients are being followed.